ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Genetic Diseases, Inborn ; Humans ; Liver/pathology* ; Liver Cirrhosis/pathology*

Probe electrospray ionization (PESI) is one of the typical types of ambient ionization technology, but its application in quantitative analysis is limited due to its poor sampling stability. Previously, we developed a new micro-pen electrospray ionization tandem mass spectrometry (μPen-ESI-MS/MS) method based on PESI. In this study, a μPen-ESI-MS/MS method to measure testosterone and dextromethorphan in liver microsome samples was developed and validated to further applicate in evaluating drug metabolism stability and CYP450 enzyme activity. A μPen-ESI-MS/MS method for detecting the CYP3A4 substrate testosterone and CYP2D6 substrate dextromethorphan in the liver microsome incubation system were developed, and the linearity, precision and accuracy of the method was validated. The validated method was further used to detect the metabolic stability of testosterone in the liver microsome incubation system. The results showed that the μPen-ESI-MS/MS had high efficiency with 0.3 min spraying time of each sample. The standard curve of the testosterone and dextromethorphan has good linearity (R² > 0.99), the intra- and inter-batch accuracy of testosterone and dextromethorphan was 95.9%-109.3% and 90.5%-107.3%, respectively; the intra- and inter-batch precision was acceptable with RSD values of 2.4%-13.5% and 3.4%-12.1%. The half-lives of testosterone and dextromethorphan in the liver microsome incubation system were 12 min and 14 min, respectively. This study provided a rapid and sensitive μPen-ESI-MS/MS method for the assay of testosterone and dextromethorphan in liver microsome samples, and provided a new strategy for the evaluation of drug metabolism stability and CYP3A4/CYP2D6 activity.

OBJECTIVES: To study the value of serum miR-922 and miR-506 expression levels in the diagnosis and prognostic assessment of childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 132 children with ALL (ALL group) and 80 healthy children (healthy control group) were prospectively selected in this study. Quantitative real-time polymerase chain reaction was used to measure the expression levels of serum miR-922 and miR-506 in both groups. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of miR-922 and miR-506 for childhood ALL. The Kaplan-Meier method was used to plot survival curves, and multivariate COX regression models were used to analyze the risk factors for poor prognosis in children with ALL. RESULTS: The ALL group had significantly higher expression levels of serum miR-922 and miR-506 than the control group ( CONCLUSIONS The expression levels of miR-922 and miR-506 are of good value in the diagnosis and prognostic assessment of childhood ALL.
Biomarkers, Tumor ; Child ; Humans ; Kaplan-Meier Estimate ; MicroRNAs/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; ROC Curve

OBJECTIVES: To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia. METHODS: A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels. RESULTS: Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage ( CONCLUSIONS Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.
Adipokines ; Chemokines ; Child ; Cytokines/metabolism* ; GPI-Linked Proteins/metabolism* ; Humans ; Hyperlipidemias ; Lectins/metabolism* ; Lipids ; Nephrotic Syndrome/drug therapy* ; Proteinuria

Objective To indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65％,69.16％ and 65.49％ of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72％,42.40％ and 18.25％ of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P＜0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P＜0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value ＜0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.

Objective: To understand the sources and characteristics of newly reported HIV/AIDS cases in Yiwu, Zhejiang province, from 2015 to 2016. Methods: From January 1, 2015 to December 31, 2016, newly reported HIV/AIDS cases in Yiwu were recruited in the study and they were asked to complete an in-depth field epidemiology questionnaire. Information related to their previous sexual behaviors and infection sources or routes were collected in the survey. The data were processed and analyzed with EpiData 3.0 and SPSS 19.0 software. Results: A total of 320 participants from 393 newly reported HIV/AIDS cases in Yiwu during this period were surveyed and recruited in the study. Most of them were males (268, 83.8%), unmarried (141, 44.1%), aged between 25-44 years (166, 51.9%), had census register in other provinces (217, 67.8%) and educational level of junior high school (128, 40.0%). Among 305 cases whose infection times could be determined, 107 (35.1%) were newly infected within one year, and among 267 cases whose infection location could be determined, 200 (74.9%) were infected in Yiwu. New infections were mainly detected in those who had homosexual behaviors or causal sex partners (during the past year) and through active detection approach. Local infections were mainly among those who had local residence and commercial heterosexual behavior in Yiwu. Conclusions: Most newly reported HIV/AIDS cases in Yiwu from 2015-2016 were infected for more than one year and locally infected. Census registration of other provinces, homosexual sexual behavior, and casual sexual behavior give major contribution to HIV/AIDS epidemic in Yiwu.
Acquired Immunodeficiency Syndrome ; Adult ; China/epidemiology* ; HIV Infections/epidemiology* ; Homosexuality, Male ; Humans ; Male ; Risk-Taking ; Sexual Behavior ; Sexual Partners ; Surveys and Questionnaires

Mongolian medicine is the traditional drug with the theory of Mongolian medicine and pharmacy as a guide, which made a great contribution to the survival and development of the Mongolian people. Mongolian medicine "Bashaga" faced the situations of origin is unclear, and clinical therapy is confused and so on. This paper summarizes the original plants and studies the species textual research and ethnopharmacology of Mongolian medicine "Bashaga". This paper intends to ensure authentic plant and provide comprehensive insight into the chemical constituents, pharmacology and application status of Mongolian medicine "Bashaga" to discuss the rationality of the confirmation in "Bashaga" authentic plant.

Objective:To explore the effect of high glucose-based peritoneal dialysis fluids on NLRP3-IL-1β in human peritoneal mesothelial cells.Methods:HMrSV5 cells (SV40 immortalized human peritoneal mesothelial cell line) were grown in type Ⅰ collagen-coated dishes in DMEM/F12 containing 10％ fetal calf serum (FCS).All experiments on HMrSV5 cells were performed between passages 5 and 10.The cells were divided into 7 groups:control,1.5％ dextrose,2.5％ dextrose,4.25％ dextrose,rotenone,thenoyltrifluoroacetone (TTFA),and antimycin A.Immunoblotting was used to evaluate the expression of IL-1 β.Small interfering RNA (siRNA) targeting NLRP3 was used to downregulate the expression of NLRP3 and Western blot was used to evaluate the expression of IL-1 β in human peritoneal mesothelial cells exposed to 4.25％ dextrose.In the meanwhile,resveratrol (RSV) was used to induce autophagy,3-methyladenine (3-MA) and siRNA against Beclin 1 or ATG5 were used to block autophagy,flow cytometric was used to analyze the respiring (mitotracker deep red),total (mitotracker green) and reactive oxygen species (ROS)-generating mitochondria (mitoSOX);Western blot was used to evaluate the expression of IL-1β.Results:The IL-1β relative expressions were 0,0.175 ±0.082,0.418 ± 0.163,2.357 ±0.288,2.642 ±0.358,3.271 ±0.462,and 0.123 ±0.091,indicating that the cells exposed to high glucose-based peritoneal dialysis fluids and cells treated with mitochondria respiratory chain key enzyme complex Ⅰ,and complex Ⅲ inhibitors increased the IL-1β expression.And we found that NLRP3 knock-down significantly blocked the upregulation of IL-1 β.In addition,the fluorescence intensity of total mitochondria and ROS-generating mitochondria in the following groups:control,negative control,RSV,3-MA,ATG5 siRNA,Beclin1 siRNA were 1.76 ± 0.42,1.83 ± 0.55,1.85 ± 0.62,7.36 ± 0.92,5.35 ± 0.77,5.06 ± 0.62 and 821.68 ± 95.12,868.15 ± 102.82,723.39 ± 92.56,1 660.08 ± 113.65,1 433.01 ± 107.24,1 562.36 ± 112.88 respectively.The increased concentrations of mitochondrial ROS and IL-1β upregulation were confirmed in the inhibition but not the induction of autophagy.We also found that downregulation of ATG5 and Beclin1 sensitized cells for the release of IL-1β induced by MSU (monosodium urate) or nigericin which was the NLRP3 inflammasome activator.RSV treatment attentuated this effect.Conclusion:Long-term application of high glucose-based peritoneal dialysis fluids can trigger the consistent activation of NLRP3-IL-1ββ in peritoneal mesothelial cells.Timely initiation of autophagy may block the NLRP3-IL-1ββ activation and provide a basis for the further development of a potential therapeutic strategy for delay of chronic inflammation and peritoneal fibrosis associated with peritoneal dialysis.

AIM To explore the curative effects,adverse events,effects on immunity function and cost-effectiveness of Aiyu Capsules (Cremastrae pseudobulbus,Solanum lyratum,Angelicae sinensis Radix,etc.) or Fufang Banmao Capsules (Mylabris,Ginseng Radix et Rhizoma,Astragali Radix,etc.) combined with icotinib hydrochloride in the treatment of advanced non-small cell lung carcinoma (NSCLC).METHODS One hundred and sixty patients with advanced NSCLC were randomly divided into three groups.The patients in icotinib hydrochloride group (n =80) took icotinib hydrochloride,125 mg each time,three times a day;the patients in Aiyu Capsules + icotinib hydrochloride group or Fufang Banmao Capsules + icotinib hydrochloride group were treated with Aiyu Capsules (40 cases,three pills each time,three times a day) or Fufang Banmao Capsules (40 cases,one pill each time,three times a day) combined with icotinib hydrochloride (125 mg each time,three times a day),respectively.Curative effects,adverse events,serum tumor markers,dendritic cell subsets and cost-effectiveness among the three groups were compared.RESULTS Eight weeks after the treatment,effective rates in the Aiyu Capsules + icotinib hydrochloride group (82.50％) and Fufang Banmao Capsules + icotinib hydrochloride group (97.5％) were significantly higher than that in the icotinib hydrochloride group (73.5％) (P ＜ 0.05).Six-month survival rates in the icotinib hydrochloride group,Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were 93.7％,97.5％ and 97.5％,respectively;one-year survival rates in the three groups were 53.7％,72.5％ and 75.0％,respectively;two-year survival rates in the three groups were 20.0％,37.5％ and 40.0％,respectively.One-year,two-year survival rates in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were significantly higher than those in the icotinib hydrochloride group (P ＜ 0.05).Myeloid dendritic cell (mDC) subsets' increases (d8week-d1) in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were significantly higher than that in the icotinib hydrochloride group (P ＜ 0.05).There was no statistical significance in plasmacytoid dendritic cell (pDC) subsets' change among the three groups (P ＞ 0.05).Changes of carcinoembryonic antigen (CEA),cytokeratin-19-fragment (CYFRA21-1),neuron-specific enolase (NSE) in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were higher than those in the icotinib hydrochloride group (P ＜ 0.05).Treatment costs in the Aiyu Capsules + icotinib hydrochloride group and Fufang Banmao Capsules + icotinib hydrochloride group were significantly lower than that in the icotinib hydrochloride group (P ＜ 0.05).No obvious statistical difference in adverse events was found among the three groups (P ＞ 0.05).CONCLUSION The curative effects and cost-effectiveness of Aiyu Capsules or Fufang Banmao Capsules combined with icotinib hydrochloride are better than those of icotinib hydrochloride alone in the treatment of advanced NSCLC.